Clinical manifestations of HIV

Clinical manifestations of HIV Emerging trends Garfield Forbes Introduction     Human immunodeficiency virus Characterized by opportunistic infections and malignancies Changing in the clinical spectrum of the disease Related to multiple factors HIV virus HAART      Protease therapy Decline in morbidity and mortality 1997 Study Pre-HAART and HAART eras Reduced viral loads and increased CD4+ cells Evolving epidemiological trends     Reduced rate of mortality decline Viral resistance Compliance Side effects linked to HAART Pathogenesis of the trends     Drug toxicity Prolonged exposure to HIV Cytokine mediated Immune changes accompanying viral suppression HAART toxicity     Mitochondrial metabolism Lactic acidosis Pancreatitis Pregnant females –Stavudine/ ddI Lactic acidosis       Abdominal pains Vomiting Nausea Hepatic steatosis Abnormal LFTS Peripheral lipoatrophy HAMMAS      HIV- associated metabolic and morphologic abnormality syndrome Insulin resistance- GLUT-4 Dyslipidemia ? PI Documented prior to HAART Skeletal changes      Osteopenia Cytokine mediated IL-2, TNF HAART increases level of TNF Interventions in high risk groups TNF TNF mechanisms Cardiovascular changes        Accelerated atherosclerosis Myocardial infarction- markedly increased risk Hypercoaguable state Vasculitis Increased VLDL/ Cholesterol Indinavir Switching therapy Haematologic changes    Cytopenias Immune thrombocytopenic purpura TTP Malignancies   Kaposi sarcoma- declining incidence Non-Hodgkins lymphoma-mixed Opportunistic infections        Reduced incidence worldwide Reporting bias PCP CMV Bacterial pneumonias Toxoplasmosis Cryptococcosis Pathogenesis of OIs      Co-pathogenesis Up regulation of HIV replication Latently infected CD4+ cells activated Increased susceptibility to de novo infections Cellular signaling by cytokines IL-6 and TNF OIs Prophylaxis   Trial following Increased CD4+ cells and reducing viral loads Antigen specific immunity lost Immune reconstitution syndromes         Early in therapy Inflammatory manifestations Low CD4+ count a high risk factor MAC Tb- Cavitary lung lesions HHV-8, CMV Fever, lymphadenitis Steroids and antimicrobials Tuberculosis    Higher prevalence Often precedes diagnosis of HIV infection Extra-pulmonary and miliary forms more common Pulmonary Tb Syphilis     Ocular Neurosyphilis CSF pleocytosis VDRL- Positive in 2/3 Herpes viruses   HHV-8 GBV-Type C Increasing viral resistance   Multiple resistant strains Implications for public health Acute HIV infection      Transient symptomatic illness Mononucleosis type symptoms Rapid viral replication Aggressive immune response Index of suspicion Acute HIV infection Acute intervention in Acute HIV infection    Early diagnosis Triple therapy Reduction in reservoirs Acute HIV intervention Acute HIV infection Acute infection Progressive multifocal leucoencephalopathy PML     Reactivation of JC virus Progressive neurological deterioration Defective oligodendrocyte and myelin maintenance PI response The wasting syndrome    Tumor necrosis factor – alpha Alteration of gut permeability GI immunologic changes Conclusion    Important in Diagnosis and early targeted interventions Public Health importance Research Thank you Thank You